TGF-beta1受体而后整合蛋白介导的两条信号转导途径的cross-talk

In this study first of all the cell model of anoikis is established. Our results showed that 10ng/ml TGF-b1 treatment could increase the expression of integrin a5 and b1 subunit at cell surface in a dose and time dependant manner. Then cell adhesion was observed after TGF-b1 treatment in SMMC-7721 cells. The results showed that cell adhesions onto Fibronectin (Fn) and Laminin (Ln) were increased. Our results from Western Blot Assay showed that after SMMC-7721 cells were treated with TGF-b1, the expression of FAK in the cells was not apparently affected, while the tyrosine phosphorylation of FAK was up regulated. It suggests that increasing phosphorylation of FAK, an important event in integrin-mediated signaling, is at least a part of signaling during TGF-b1-induced migration, if it is not required for the initiation of cell migration. Furthermore, the increase in FAK phosphorylation may due to the decrease in dephosphorylation. PTEN could also modulate cell migration and invasion by regulating the signals generated at the focal adhesions, through the direct inactivation of FAK. The results showed that the expression of PTEN was downregulated by TGF-b1 treatment in a dose and time dependant manner, and it supported our idea that TGF-b1 modulated FAK phosphorylation may partly through the decrease of PTEN expression..Together, our observations about the effect of TGF-b1 on integrin expression and integrin-mediated signal transduction in SMMC-7721 cells showed that TGF-b1 increased the expression of a5b1 integrin on protein and mRNA level, enhanced cell adhesion onto Fn and Ln, and promoted cell migration, which might through increasing cell adhesion, and FAK phosphorylation by upregulating integrin expression or downregulating PTEN, a novel tumor suppressor and phosphatase.

细胞赖以生存的信号转导途径在细胞内可形成网络结构，是细胞对外界众多信号作出综合反应的分子基础。本项目通过分别启动TGF-beta1受体或整合蛋白介导的信号传导途径，观察粤硪惶跬揪吨兄匾藕欧肿拥幕虮泶锛氨泶锊锪姿峄挠跋欤⒁韵赴蛲鲎魑δ鼙浠闹副辏越沂綯GF-beta1受体和整合蛋白介导的两条信号转导途径的cross-talk.